NCT00600938

Brief Summary

This is a clinical research study in patients who have iron overload in the heart due to chronic blood transfusions. The study will have 2 treatment groups and will compare the safety and efficacy of chelation therapy with a medicine called deferasirox (ICL670) with another medicine called deferoxamine (DFO). The study is aimed at finding out which of the two medicines is the best for treating iron overload in the heart. Patients will be treated for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study treatment in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the heart and the liver will be evaluated using specific magnetic resonance imaging (MRI) assessments.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
197

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Nov 2007

Longer than P75 for phase_2

Geographic Reach
11 countries

21 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2007

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 14, 2008

Completed
11 days until next milestone

First Posted

Study publicly available on registry

January 25, 2008

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

August 27, 2014

Completed
Last Updated

August 27, 2014

Status Verified

August 1, 2014

Enrollment Period

5.3 years

First QC Date

January 14, 2008

Results QC Date

February 21, 2014

Last Update Submit

August 13, 2014

Conditions

Transfusional Iron OverloadTransfusional Hemosiderosis

Keywords

iron overloadcardiac ironhaemosiderosismyocardial T2*left ventricular ejection fractionLVEFcardiac dysfunctionthalassaemiaDiamond Blackfan anemiaDBAsideroblastic anemiamyelodysplastic syndromesMDS (low and INT-1 risk as per the IPSS for MDS)liver MRIdeferasiroxdeferoxamineICL670DFOcardiovascular magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

  • Core Study: Change From Baseline in Myocardial T2* (Magnetic Resonance T2-star (T2*) Technique for the Measurement of Tissue Iron) After 12 Months Treatment

    Non- inferiority in efficacy of deferasirox compared to deferoxamine (DFO) in treating cardiac iron overload as measured by T2\*. A non-inferiority margin of 0.9 (90%) was applied. Due to limitations in performing heart biopsies, T2\* (T2 star), a Magnetic Resonance (MR) relaxation parameter expressed in milliseconds, as is an important tool to noninvasively quantify cardiac iron concentration. Studies have shown that myocardial T2\* evaluations may predict cardiac events, e.g., impaired (\<56%) left ventricular ejection fraction (LVEF) is prevalent among patients with low T2\*: found in 62% of patients with T2\*\<8 ms; 20% with T2\* of 8-12 ms; and in 5% with T2\* \>12 ms (Tanner 2006)

    12 Month

Secondary Outcomes (20)

  • Core Study: Cardiac Function After 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)

    12 Month

  • Core Study: Cardiac Function After 6 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular Ejection Fraction (LVEF)

    6 Month

  • Core Study: Change From Baseline in Myocardial T2* After 6 Months Treatment

    6 Month

  • Core Study: Cardiac Function After 6 and 12 Months Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Systolic Volume Indices (LVESVI)

    6 Month, 12 Month

  • Core Study: Core Study: Cardiac Function After 6 and 12 Months of Treatment With Deferasirox vs. Deferoxamine, by Change in Left Ventricular End Diastolic Volume Indices (LVEDVI)

    6 Month, 12 Month

  • +15 more secondary outcomes

Study Arms (4)

Deferasirox

EXPERIMENTAL

20 mg/kg/day once daily (od) for 2 weeks, followed by 30 mg/kg/day od for 1 week and a subsequent continuation of 40 mg/kg/day

Drug: Core Study: DeferasiroxDrug: Deferasirox

Deferasirox Placebo

ACTIVE COMPARATOR

50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week

Drug: Core Study: DeferoxamineDrug: Deferoxamine

Extension: deferoxamine to deferasirox

EXPERIMENTAL

"DFO to ICL" (patients who switched from DFO to deferasirox in extension)

Drug: Extension: deferoxamine to deferasirox

Extension: deferasirox to deferoxamine

EXPERIMENTAL

"ICL to DFO" (patients who switched from deferasirox to DFO in extension)

Drug: Extension: deferasirox to deferoxamine

Interventions

Core Study: DeferasiroxDRUG

20 mg/kg/day once daily (od) for 2 weeks, followed by 30 mg/kg/day od for 1 week and a subsequent continuation of 40 mg/kg/day

Also known as: "ICL to ICL"
Deferasirox
Core Study: DeferoxamineDRUG

50 mg/kg/day to 60 mg/kg/day infused subcutaneously in 8- to 12-hour intervals administered 5 to 7 days/week

Also known as: "DFO to DFO"
Deferasirox Placebo
Extension: deferoxamine to deferasiroxDRUG

40 mg/kg deferasirox once daily administered 30 minutes before taking food.

Also known as: "DFO to ICL"
Extension: deferoxamine to deferasirox
Extension: deferasirox to deferoxamineDRUG

DFO at a target range of 50 mg/kg/day to 60 mg/kg/day via subcutaneous (sc) infusion lasting a period of 8 to 12 hrs administered for 5 to 7 days per week,

Also known as: "ICL to DFO"
Extension: deferasirox to deferoxamine
DeferasiroxDRUG
Deferasirox
DeferoxamineDRUG
Deferasirox Placebo

Eligibility Criteria

Age10 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female patients, aged 10 years and above, with β-thalassemia major or DBA or sideroblastic anemia on chronic transfusion therapy, having given written consent to participate in the study.
  • Patients with cardiac iron as measured by a myocardial T2\* value that is ≥ 6ms but not ≥ 20 ms.
  • Patients with a lifetime history of at least 50 units of red cell transfusions, and must be receiving at least ≥10 units/yr of red blood cells transfusions.
  • Patients with a left ventricular ejection fraction (LVEF) ≥ 56 % as determined by cardiovascular magnetic resonance (CMR).
  • Patients with liver iron content (LIC) value ≥ 3 mg Fe / g dw, as determined by liver MRI.

You may not qualify if:

  • Patients with clinical symptoms of cardiac dysfunction.
  • Patients unable to undergo study assessments including MRI
  • Patients participating in another clinical trial or receiving an investigational drug.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Novartis Investigative Site

Toronto, Ontario, M5G 1X8, Canada

Location

Novartis Investigative Site

Nanning, Guangxi, 530021, China

Location

Novartis Investigative Site

Limassol, 3304, Cyprus

Location

Novartis Investigative Site

Al Mansurah, Egypt

Location

Novartis Investigative Site

Cairo, Egypt

Location

Novartis Investigative Site

Cagliari, CA, 09121, Italy

Location

Novartis Investigative Site

Genova, GE, 16128, Italy

Location

Novartis Investigative Site

Hazmiyeh, Lebanon

Location

Novartis Investigative Site

Taipei, Taiwan, 10002, Taiwan

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Adana, Turkey, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, Turkey, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, Turkey, 35040, Turkey (Türkiye)

Location

Novartis Investigative Site

Antalya, 07070, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Dubai, Dubai, 9115, United Arab Emirates

Location

Novartis Investigative Site

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

Location

Novartis Investigative Site

London, N19 5NF, United Kingdom

Location

Novartis Investigative Site

London, NW1 2PJ, United Kingdom

Location

Related Publications (2)

  • Pennell DJ, Porter JB, Piga A, Lai YR, El-Beshlawy A, Elalfy M, Yesilipek A, Kilinc Y, Habr D, Musallam KM, Shen J, Aydinok Y; CORDELIA study investigators. Sustained improvements in myocardial T2* over 2 years in severely iron-overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine. Am J Hematol. 2015 Feb;90(2):91-6. doi: 10.1002/ajh.23876. Epub 2014 Nov 19.

    PMID: 25345697DERIVED

  • Pennell DJ, Porter JB, Piga A, Lai Y, El-Beshlawy A, Belhoul KM, Elalfy M, Yesilipek A, Kilinc Y, Lawniczek T, Habr D, Weisskopf M, Zhang Y, Aydinok Y; CORDELIA study investigators. A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in beta-thalassemia major (CORDELIA). Blood. 2014 Mar 6;123(10):1447-54. doi: 10.1182/blood-2013-04-497842. Epub 2014 Jan 2.

    PMID: 24385534DERIVED

MeSH Terms

Conditions

Iron OverloadHemochromatosisThalassemiaAnemia, Diamond-BlackfanAnemia, SideroblasticMyelodysplastic Syndromes

Interventions

DeferasiroxDeferoxamine

Condition Hierarchy (Ancestors)

Iron Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesMetal Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesAnemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesAnemia, Hypoplastic, CongenitalAnemia, AplasticRed-Cell Aplasia, PureCongenital Bone Marrow Failure SyndromesBone Marrow Failure DisordersBone Marrow Diseases

Intervention Hierarchy (Ancestors)

BenzoatesAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHydroxamic AcidsHydroxylaminesAminesHydroxy Acids

Results Point of Contact

Title
Study Director
Organization
Novartis Pharnaceuticals
trialandresults.registries@novartis.com
862-778-8300

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 14, 2008

First Posted

January 25, 2008

Study Start

November 1, 2007

Primary Completion

March 1, 2013

Study Completion

March 1, 2013

Last Updated

August 27, 2014

Results First Posted

August 27, 2014

Record last verified: 2014-08

Locations

LE(1)AE(1)GB(4)CY(1)TW(1)CN(1)IT(2)TH(2)TU(5)EG(2)CA(1)